The tetracyclic structure of indolo[3,2-b]quinolines, also referred to as quindoline (1) constitutes an important structural moiety in the literature because of its effect on numerous biological functions [a) Dwuma-Badu, D.; Ayim, 1. S.; Fiagbe, N. 1.; Knapp, 1. E.; Schiff P. L.; Jr, Slatkin D. J. J. Pharm. Sci. 1978,67,433-434. b) Ablordeppey, S. Y.; Hufford, C. D.; Borne, R. F.; Dwuma-Badu, D. Planta Med. 1990, 56, 416. c) Cimanga K.; De Bruyne T.; Lasure A; Van Poel, B.; Pieters, L.; Claeys, M.; Vanden Berghe, D.; Kambu, K.; Tona, L.; Vlietinck, A 1. Planta Medica, 1996, 62,22-27. d) Ablordeppey, S. Y.; Fan, P.; Ablordeppey, 1. H.; Mardenborough, L. Curr Med. Chem. 1999, 6, 1151-1195]. For example, cryptolepine (2a & b) and several of its analogs display antiaggregatory [a) Oyekan, A O.; Ablordeppey, S. Y Gen. Pharmacol. 1993, 24, 1285-1290. b) Oyekan, A O.; Ablordeppey, S. Y Gen. Pharmacol., 1993,24,461-469. c) Oyekan A O.; Ablordeppey S. Y Med. Chem. Res. 1996, 6, 602-610. d) Singh, M.; Singh, M. P.; Ablordeppey, S. Drug Dev Ind Pharm 1996, 22,377-381], antihypertensive [Noamesi, B. K.; Bamgbose, S. O. A. Planta Med 1980,39,51-56], antihyperglycemic [Bierer D. E.; Fort D. M.; Mendez C. D.; Luo 1.; Imbach P. A; Dubenko L. G.; Jolad S. D.; Gerber, R. E.; Litvak, 1.; Lu Q.; Zhang P.; Reed M. 1.; Waldeck N.; Bruening R. C.; Noamesi B. K.; Hector R. F.; Carlson T. J.; King S. R. J Med Chem. 1998,41,894-901], antibacterial [Boakye-Yiadom, K.; Heman-Ackah, S. M. J Pharm Sci 1979, 68,1510-1514. Sawer, 1. K.; Berry M. 1.; Brown M. W.; Ford, J. L. J Applied Bacteriol, 1995, 79,314-321], anticancer [Dassonneville, L.; Lansiaux, A; Wattelet, A; Wattez, N.; Mahieu, C.; Van Miert, S.; Pieters L.; Bailly, C. Eur J Pharmacol 2000, 409, 9-18], antimalarial [a) Cimanga, Kanyanga; De Bruyne, Tess; Pieters, Luc; Vlietinck, Arnold J.; Turger, Caesar A. J Nat Prod 1997, 60, 688-691. b) Wright, C. W.; Phillipson, J. D.; Awe, S. 0.; Kirby, G. c.; Warhurst, D. C.; Quetin-Leclercq, J.; Angenot, L. Phytother Res 1996, 10, 361-363. c) Grellier, P.; Ramiaramanana, L.; Millerioux, V.; Deharo, E.; Schrevel, J.; Frappier, F.; Trigalo, F.; Bodo, B.; Pousset, J.-L. Phytother Res, 1996, 10, 317-321. d) Kirby, G. C.; Paine, A; Warhurst, D. C.; Noamesi, B. K; Phillipson, J. D. Phytother Res, 1995, 9,359-63], activities among others.
A unified mechanism by which the drug produces the different biological activities has not been elucidated. However, cryptolepine has been shown to bind to DNA fragments [Lisgarten, J. N.; Pous, J.; ColI, M.; Wright, C. W.; Aymami, J. Acta Crystallogr D BioI Crystallogr, 2002, D58, 312-313] in a rather unique fashion. Furthermore, it intercalates DNA and stimulates topoisomerase II mediated cutting of DNA [a) Dassonneville L.; Bonjean K; De Pauw-Gillet, M.-C.; Colson P.; Houssier, C.; QuetinLeclercq, 1; Angenot, L.; Bailly, C. Biochemistry, 1999, 38, 7719-26. b) Bailly, C.; Laine, W.; Baldeyrou, B.; De Pauw-Gillet, M.-C.; Colson, P.; Houssier, C.; Cimanga, K; Van Miert, S.; Vlietinck, A J.; Pieters, L. Anticancer Drug Des, 2000, 15, 191-201. c) Bonj ean, K.; De PauwGillet, M.-C.; Defresne, P.; Colson P.; Houssier, c.; Dassonneville L.; Bailly, C.; Greimers, R.; Wright, c.; Quetin-Leclercq, J.; Tits, M.; Angenot, L. Biochemistry, 1998, 37, 5236-5146. d) Dassonneville, L.; Lansiaux, A; Wattelet, A; Wattez, N.; Mahieu, c.; Van Miert, S.; Pieters L.; Bailly, C. Eur J Pharmacol, 2000, 409, 9-18]. More recently, cryptolepine has been identified as a potential inhibitor of telomerase and a G-quadruplex DNA stabilizing agent [Guyen, B.; Schultes, C. M; Hazel, P.; Mann, J.; Neidle, S. Org Biomol Chem, 2004, 2, 981-8].
The structures of quindoline and its basic and salt forms are:

It has been shown that alkylation of the N-5 atom in quindoline is necessary for several of the therapeutic activities associated therewith [a) Ablordeppey, S. Y.; Fan, P.; Clark, A. M.; Nimrod, A Bioorg Med Chem, 1999, 7, 343-349. b) Mardenborough L. G.; Fan, P. c.; Ablordeppey, S. Y.; Nimrod, A; Clark A M. Med Chem Res, 1999,9, 118-132. c) Oyekan, A. O.; Ablordeppey, S. Y. Med Chem Res 1996, 6,602-610]. In particular, it has been reported that co-phenylpentyl and co-cyclohexylpentyl moieties on the N-5 atom of the quindoline ring produce a high antifungal potency and broadens the spectrum of activities. It is interesting to note that N-5 alkylation produces an anhydronium base in which the N-5 nitrogen becomes positively charged, i.e., aromatic quaternary nitrogen (2b), under acidic conditions but reverts to Sp3 type nitrogen under basic conditions (2a). This physical characteristic of cryptolepine is also accompanied by a color change from pink in a basic medium to orange in an acidic environment. This unique behavior may allow for easy entry into cells in the basic form, despite its quaternary nature, and yet produce its pharmacological effect in the salt form.
It is an object of the present invention to provide novel quindoline compounds having one or more of a variety of therapeutic properties.